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Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’ – Authors’ reply

We would like to reply to the letter by Dolff and colleagues [1] regarding our article in a recent issue of Arthritis Research & Therapy [2]. We thank the authors for their interest in our work and the critical reading of our article. The aim of our study was to investigate a possible association between the IFN type I signature and memory T helper 17 (Th17) cells and their cytokines in systemic lupus erythematosus (SLE). Since CCR6 can be expressed by regulatory T (Treg) cells, we have excluded CD25high cells to discriminate between CD4+CD45RO+CCR6+CD25 (primary Th17 cells) and Treg cells. Concerning the observation on co-expression of IL-17A with IFN-γ, we would like to remark that IFN-γ is an IFN type II, and not an IFN type I, cytokine and does not bind to the IFN type I receptor. Detection of IFN type I activity is hampered by the difficulty to assess the different subtypes of this cytokine. Therefore, analysis of IFN type I-induced gene expression in RNA from peripheral blood cells, the so-called IFN type I signature, is used as a measure for IFN type I activity. Although we fully agree with the authors that the relationship between Th cells and IFN type I deserves further study, their remark on the ‘genetic’ signature is confusing and probably refers to the IFN type I-induced gene expression signature, which is detected at the RNA level.

The relationship between CD25+ Tregs and IFN type I is certainly of interest for further study as these Tregs are carrying the IFN type I receptor and thus respond to increased systemic IFN type I activity in SLE. Also, follow-up studies with a focus on adaptive and innate cells producing IL-17, including the relation with IL-21 and IL-22 and plasticity, will be of interest [3, 4]. In our article, we presented data supporting a potential co-activity between IFN type I and CD4+memory CCR6+ Th17 cytokines. Further studies are needed to confirm this co-activity with a focus on revealing the mechanism of this dangerous link in SLE.

Abbreviations

IFN:

Interferon

IL:

Interleukin

SLE:

Systemic lupus erythematosus

Th17:

T helper 17

Treg:

Regulatory T.

References

  1. 1.

    Dolff S, Abdulahad WH, Kallenberg CGM: Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’. Arthritis Res Ther. 2014, 16: 409-10.1186/ar4576.

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Correspondence to Erik Lubberts.

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The authors declare that they have no competing interests.

Marjan A Versnel and Erik Lubberts contributed equally to this work.

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Brkic, Z., Corneth, O.B., Versnel, M.A. et al. Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’ – Authors’ reply. Arthritis Res Ther 16, 410 (2014). https://doi.org/10.1186/ar4578

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Keywords

  • Systemic Lupus Erythematosus
  • Interferon
  • Th17 Cell
  • Treg Cell
  • Expression Signature